The overall objective of this project is to exploit the transgenic mouse system by introducing natural or manipulated gene sequences into the germline of an animal and to alter its phenotype and genetic background. This system provides a new way of investigating tissue specific and developmental stage specific regulation of gene expression. The current research is focused on three classes of genes that may be associated, initially, with the multistage process of murine liver tumorigenesis: (1) cytochrome P-450 genes involved in metabolic activation of chemical carcinogens; (2) the known oncogenes, myc, ras and SV40 large T antigen, and (3) the developmental expression of a family of genes that contain sequences homologous to the Drosophilia homebox. At present the work has involved setting up the transgenic mouse system.